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Systematic investigation of cellular response and pleiotropic effects in atorvastatin-treated liver cells by MS-based proteomics
- Source :
- Journal of proteome research. 14(3)
- Publication Year :
- 2015
-
Abstract
- For decades, statins have been widely used to lower cholesterol levels by inhibiting the enzyme HMG Co-A reductase (HMGCR). It is well-known that statins have pleiotropic effects including improving endothelial function and inhibiting vascular inflammation and oxidation. However, the cellular responses to statins and corresponding pleiotropic effects are largely unknown at the proteome level. Emerging mass spectrometry-based proteomics provides a unique opportunity to systemically investigate protein and phosphoprotein abundance changes as a result of statin treatment. Many lipid-related protein abundances were increased in HepG2 cells treated by atorvastatin, including HMGCR, FDFT, SQLE, and LDLR, while the abundances of proteins involved in cellular response to stress and apoptosis were decreased. Comprehensive analysis of protein phosphorylation demonstrated that several basic motifs were enriched among down-regulated phosphorylation sites, which indicates that kinases with preference for these motifs, such as protein kinase A and protein kinase C, have attenuated activities. Phosphopeptides on a group of G-protein modulators were up-regulated, which strongly suggests that cell signal rewiring was a result of the effect of protein lipidation by the statin. This work provides a global view of liver cell responses to atorvastatin at the proteome and phosphoproteome levels, which provides insight into the pleiotropic effects of statins.
- Subjects :
- Proteomics
Statin
medicine.drug_class
Atorvastatin
Biology
Protein lipidation
Biochemistry
Mass Spectrometry
medicine
Humans
Protein phosphorylation
cardiovascular diseases
Protein kinase A
Liver cell
Anticholesteremic Agents
nutritional and metabolic diseases
General Chemistry
Hep G2 Cells
Cell biology
Liver
HMG-CoA reductase
biology.protein
lipids (amino acids, peptides, and proteins)
medicine.drug
Subjects
Details
- ISSN :
- 15353907
- Volume :
- 14
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of proteome research
- Accession number :
- edsair.doi.dedup.....b7d1704335f8532a1a7fb0f9af4636b6